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Translational and Clinical Research
Article first published online: 30 DEC 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 12, pages 2217–2228, December 2010
How to Cite
Kim, S. M., Oh, J. H., Park, S. A., Ryu, C. H., Lim, J. Y., Kim, D.-S., Chang, J. W., Oh, W. and Jeun, S.-S. (2010), Irradiation Enhances the Tumor Tropism and Therapeutic Potential of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Secreting Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Glioma Therapy. STEM CELLS, 28: 2217–2228. doi: 10.1002/stem.543
Author contrubutions: S.M.K.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, financial support; J.H.O.: collection and/or assembly of data, data analysis and interpretation; S.A.P.: collection and/or assembly of data; C.H.R.: data analysis and interpretation; J.Y.L.: data analysis and interpretation; D.-S.K. collection and/or assembly of data; J.W.C.: provision of study material, data analysis and interpretation; W.O.: provision of study material; S.-S.J.: conception and design, data analysis and interpretation, final approval of manuscript, financial support.
First published online in STEM CELLS EXPRESS October 13, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 30 DEC 2010
- Article first published online: 30 DEC 2010
- Accepted manuscript online: 13 OCT 2010 09:12AM EST
- Manuscript Accepted: 30 SEP 2010
- Manuscript Received: 28 MAY 2010
- National R&D Program for Cancer Control. Grant Number: 0820040
- Korea Healthcare Technology R&D Project. Grant Number: A091309
- Ministry for Health, Welfare and Family Affairs, Republic of Korea, and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology. Grant Number: 2010-0021527
- Umbilical cord blood-derived mesenchymal stem cells;
- Gene therapy
Irradiation is a standard therapy for gliomas and many other cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer gene therapy. Here, we show that tumor irradiation enhances the tumor tropism of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and the therapeutic effect of TRAIL delivered by UCB-MSCs. The sequential treatment with irradiation followed by TRAIL-secreting UCB-MSCs (MSC-TRAIL) synergistically enhanced apoptosis in either TRAIL-sensitive or TRAIL-resistant glioma cells by upregulating the death receptor 5 and by inducing caspase activation. Migration assays showed greater MSC migration toward irradiated glioma cells and the tumor site in glioma-bearing mice compared with unirradiated tumors. Irradiated glioma cells had increased expression of interleukin-8 (IL-8), which leads to the upregulation of the IL-8 receptor on MSCs. This upregulation, which is involved in the migratory capacity of UCB-MSCs, was confirmed by siRNA inhibition and an antibody-neutralizing assay. In vivo survival experiments in orthotopic xenografted mice showed that MSC-based TRAIL gene delivery to irradiated tumors had greater therapeutic efficacy than a single treatment. These results suggest that clinically relevant tumor irradiation increases the therapeutic efficacy of MSC-TRAIL by increasing tropism of MSCs and TRAIL-induced apoptosis, which may be a more useful strategy for cancer gene therapy. STEM CELLS 2010;28:2217–2228